Lecture 12 -Cell signaling II.pdfsssaajaja

Signaling

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Cellularsignaling II

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CONCEPT 9.3: Transduction: Cascades of molecular
interactions transmit signals from receptors to relay
molecules in the cell
•Cell signaling is usually
a multistepprocess
•Multistep pathways can
greatly amplifya signal
•Multistep pathways
provide more
opportunities for
coordinationand
regulationof the cellular
response

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Signal Transduction Pathways
•The binding of a signaling molecule to a receptor
triggers the first step in a chain of molecular
interactions
•The activated receptor activates another protein,
which activates another, and so on, until the protein
producing the response is activated
•At each step, the signal is transduced into a
different form, commonly a shape change in a
protein

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Protein Phosphorylation and
Dephosphorylation
•Phosphorylation and dephosphorylationof proteins
are commonly used in cells to regulate protein
activity
•Protein kinasestransfer phosphates from A T P to
protein, a process called phosphorylation
•Many relay molecules in signal transduction
pathways are protein kinases, creating a
phosphorylation cascade

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Figure 9.10

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•Protein phosphatasesrapidly remove the
phosphates from proteins, a process called
dephosphorylation
•This phosphorylation and dephosphorylation
system acts as a molecular switch, turning activities
on and off, or up or down, as required

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Small Molecules and Ions as Second
Messengers
•Many signaling pathways involve second
messengers
•These are small, non-protein, water-soluble
molecules or ions that spread throughout a cell by
diffusion
•Second messengers participate in pathways
initiated by G P C R s and R T K s
•Cyclic A M P and calcium ions are common second
messengers

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Cyclic A M P
•Cyclic A M P (c A M P), a small molecule produced
from A T P, is one of the most widely used second
messengers
•Adenylyl cyclase, an enzyme in the plasma
membrane, converts A T P to c A M P in response to
an extracellular signal

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Figure 9.11
Production of cAMP

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•Many signal molecules trigger formation of c A M P
•Other components of c A M P pathways are G
proteins, G protein-coupled receptors, and protein
kinases
•c A M P usually activates protein kinase A, which
phosphorylates various other proteins
•Further regulation of cell metabolism is provided by
G protein systems that inhibit adenylyl cyclase

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Figure 9.12
Cholera toxin
Can't breakdown GTPàALWAYS ON!
(↑ Na loss)

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Calcium Ions and Inositol Triphosphate (I P3)
•Calcium ions (Ca2+) are used widely as a second
messenger; even more so than c A M P
•Ca2+can function as a second messenger because
its concentration in the cytosol is normally much
lower than the concentration outside the cell
•A small change in number of calcium ions thus
represents a relatively large percentage change in
calcium concentration

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Figure 9.13

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•A signal relayed by a signal transduction pathway
may trigger an increase in calcium in the cytosol
•Pathways leading to the release of calcium involve
inositol triphosphate (I P3)and diacylglycerol
(D A G)as additional second messengers
•These two are produced by cleavage of a certain
kind of phospholipid in the plasma membrane

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Figure 9.14

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Nuclear and Cytoplasmic Responses
•Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
•The response may occur in the nucleus or in the
cytoplasm
•Many signaling pathways regulate the synthesis of
enzymes or other proteins, usually by turning genes
on or off in the nucleus
•The final activated molecule in the signaling
pathway may function as a transcription factor

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Figure 9.15

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•Other pathways may regulate the activity of
proteins rather than their synthesis (a cytoplasmic
response)
•For example, a signal could cause opening or
closing of an ion channel in the plasma membrane
or a change in the activity of a metabolic enzyme

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Figure 9.16Amplification of the signal & response

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The Specificity of Cell Signaling and
Coordination of the Response
•Different kinds of cells have different collections of
proteins
•These different proteins allow cells to detect and
respond to different signals
•The same signal can have different effects in cells
with different proteins and pathways
•Pathway branching and “cross-talk” further help the
cell coordinate incoming signals

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Figure 9.17

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Termination of the Signal
•Inactivationmechanisms are an essential aspect of
cell signaling
•If the concentration of external signaling molecules
falls, fewer receptors will be bound
•Unbound receptors revert to an inactive state

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Which gives the most complete and correct description
of a signal transduction pathway?
a)binding of a signal molecule to a cell protein
b)catalysis mediated by an enzyme
c)sequence of changes in a series of molecules resulting
in a response
d)binding of a ligand on one side of a membrane that results
in a change on the other side
e)the cell’s detection of a chemical or mechanical stimulus

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Which gives the most complete and correct description
of a signal transduction pathway?
a)binding of a signal molecule to a cell protein
b)catalysis mediated by an enzyme
c)sequence of changes in a series of molecules resulting
in a response
d)binding of a ligand on one side of a membrane that results
in a change on the other side
e)the cell’s detection of a chemical or mechanical stimulus